Search

A close collaboration between ophthalmologists and a reproductive endocrinology and infertility team is the ideal model for taking care of patients interested in assisted reproductive technology and preimplantation genetic testing for preventing the transmission of inherited eye diseases.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age. Although women with PCOS are often identified when presenting for oligomenorrhea or infertility care, PCOS is also linked to several metabolic morbidities, which may predispose to poor reproductive outcomes. Research has also suggested a possible independent association between PCOS and miscarriage, although available data are conflicting. This review focuses on the current literature regarding the risk of miscarriage and recurrent pregnancy loss in women with PCOS. First, we give an overview of the prevalence of miscarriage and recurrent pregnancy loss in this population and identify study limitations that contribute to the conflicting data regarding the potential association. Subsequently, we review the current literature on obesity, insulin resistance and hyperinsulinemia, thrombophilia, hyperandrogenism, oocyte, and embryo quality and viability, endometrial receptivity, oxidative stress and chronic inflammation, in addition to the efficacy of potential risk-mitigating interventions for miscarriage in women with PCOS.

To survey practice patterns designed to increase access to infertility care and evaluate the exposure of obstetrics and gynecology residents to infertility care for the underserved.

The impact of estrogen supplementation during the follicular/proliferative phase on the endometrial lining thickness (EMT) prior to intrauterine insemination (IUI) remains largely unstudied. Our study examined changes in EMT and rates of clinical pregnancy, miscarriage, and live birth for all patients who completed an IUI cycle at Stanford Fertility Center from 2017–2023 (n = 2281 cycles). Cycles with estradiol supplementation (n = 309) were compared to reference cycles without supplementation (n = 1972), with the reference cohort further categorized into cycles with a pre-ovulatory EMT of < 7 mm (“thin-lining”, n = 536) and ≥ 7 mm (“normal-lining”, n = 1436). The estradiol group had a statistically significant greater change in EMT from baseline to ovulation compared to the thin-lining reference groups (2.4 mm vs 1.9 mm, p < =0.0001). Similar rates of clinical pregnancy and live birth were observed. After adjusting for age, BMI, race/ethnicity, infertility diagnosis, and EMT at trigger, the estradiol cohort had a significantly increased odds of miscarriage versus the entire reference cohort (2.46, 95 % confidence interval [1.18, 5.14], p = 0.02). Thus, although estradiol supplementation had a statistically significant increase in EMT compared to IUI cycles with thin pre-ovulatory EMT (<7 mm), this change did not translate into improved IUI outcomes such as increased rates of clinical pregnancy and live birth or decreased rate of miscarriage. Our study suggests that supplemental estradiol does not appear to improve IUI outcomes.

To assess the impact of low estradiol (E2) levels in letrozole-stimulated frozen embryo transfer (FET) cycles on pregnancy and neonatal outcomes.

To compare the pregnancy outcomes of lesbian women undergoing donor sperm intrauterine insemination (IUI) with that of heterosexual women undergoing IUI using partner or donor sperm.

Uterine fibroids are a common finding in infertility patients. Impaired implantation and decidualization have been proposed to contribute to compromised fertility. Data are limited on the endometrial transcriptome from subjects with uterine fibroids, as well as endometrial receptivity and decidualization potential of endometrial stromal fibroblasts (eSF) from women with fibroids. Our objective was to investigate the endometrial transcriptome of women with noncavity-distorting intramural fibroids and compare them to control subjects with no uterine pathology throughout the menstrual cycle. We also evaluated endometrial receptivity gene expression and basic endometrial functions such as decidualization, proliferation, and apoptosis in women with fibroid uterus. Results showed that large numbers of transcripts were significantly dysregulated throughout the menstrual cycle in fibroid subjects compared to controls. However, there were essentially no differences in the expression of receptivity markers at the tissue level, as well as decidualization markers in tissue and eSF in subjects with fibroids compared to controls. However, eSF from women with a fibroid uterus exhibited decreased proliferation potential and increased apoptosis upon decidualization. These data indicate preserved implantation and decidualization potential despite observed gene expression changes in endometrium from women with noncavity-distorting fibroids compared to controls. How this phenomenon and altered proliferation/apoptosis may contribute to impairment of endometrial function in subfertile patients warrants further investigation.Decidualization and implantation potentials are not affected in the endometrium of women with noncavity-distorting fibroids compared to controls, despite a large number of differentially regulated genes.

In this report, we describe abrupt onset of secondary amenorrhea in a woman with history of chronic systemic sarcoidosis. Endocrinologic evaluation of her hypothalamic-pituitary axis revealed abnormally low levels of follicle-stimulating hormone, luteinizing hormone, and insulinlike growth factor 1 and elevated prolactin. Urine osmolality was low, and serum osmolality was high. Magnetic resonance imaging revealed diffuse extensive leptomeningeal enhancement, with involvement of the hypothalamus, pituitary stalk, and the optic chiasm. Clinical diagnosis was consistent with neurosarcoidosis with hypothalamic-pituitary infiltration resulting in clinical hypogonadotropic hypogonadism, hyperprolactinemia, and diabetes insipidus. In our report, we provide an overview of basic reproductive neuroendocrinology and discuss salient concepts of the pathogenesis, clinical manifestations, evaluation, and management of hypogonadotropic hypogonadism. The current literature on neurosarcoidosis with involvement of the hypothalamic-pituitary axis is summarized. The possibility of infiltrative process should be considered in patients with new diagnosis of hypogonadotropic hypogonadal amenorrhea.

Purpose To investigate expression of molecular transporters and CYP4B1 in endometrium from women with and without endometriosis.Methods Expression of genes encoding proteins: ATP-binding cassette sub-family G member 1 (ABCG1), aquaporin 3 (AQP3), solute carrier family 16, member 6 (monocarboxylic acid transporter 7) (SLC16A6), and transmembrane emp24 protein transport domain containing 6 (TMED6), as well as a member of the cytochrome P450 family 4 subfamily B, polypeptide 1 (CYP4B1) were assessed by quantitative (Q)RT-PCR in proliferative (PE) and early secretory (ESE) endometrium from 27 normoovulatory women with and without endometriosis. Cellular localization of these proteins was determined by immunohistochemistry.Results In eutopic endometrial tissue from women without endometriosis, mRNA expression of ABCG1, CYP4B1, and SLC16A6 was significantly up-regulated in the PE to ESE transition. CYP4B1 mRNA in endometrium from women with disease increased significantly compared to samples from women without disease, while there was no change in ABCG1 and SLC16A6 mRNA levels. However, immunodetection of ABCG1, AQP3, and TMED6 was similar across cycle phases, and there was no significant difference in immunostaining intensity or localization between women with and without endometriosis.Conclusions Molecular transporters and CYP4B1 are expressed in human endometrium, and a role for transporters and CYP4B1 in normal endometrial function and in women with endometriosis remains to be determined.

To review the recent literature on the involvement and importance of leukemia inhibitory factor (LIF) in the human implantation process, and the attempts using LIF-based interventions to improve assisted reproductive technologies (ARTs) outcome in women with recurrent implantation failure.

The cellular sources that contribute to the renewal of human endometrium are largely unknown. It has been suggested that endometrial stem cells originate from bone marrow-derived mesenchymal stem cells (MSC), with subsequent development into endometrial stromal fibroblasts (hESF). We hypothesized that if bone marrow-derived MSC contribute to endometrial regeneration and are progenitors of hESF, their treatment with agents known to regulate hESF differentiation could promote their differentiation down the stromal fibroblast lineage. To this end, we treated bone marrow-derived MSC with estradiol and progesterone, bone morphogenetic protein 2 (BMP2), and activators of the protein kinase A (PKA) pathway and investigated specific markers of hESF differentiation (decidualization). Furthermore, we investigated the transcriptome of these cells in response to cAMP and compared this to the transcriptome of hESF decidualized in response to activation of the PKA pathway. The data support the idea that MSC can be differentiated down the hESF pathway, as evidenced by changes in cell shape and common expression of decidual markers and other genes important in hESF differentiation and function, and that bone marrow-derived MSC may be a source of endometrial stem/progenitor cells. In addition, we identified MSC-specific markers that distinguish them from other fibroblasts and, in particular, from hESF, which is of biologic relevance and practical value to the field of endometrial stem cell research.

To present the framework for Stanford Fertility and Reproductive Health’s comprehensive reproductive biobanking initiatives and results of first year of recruitment.

To investigate if any of the World Health Organization semen parameters and/or male age are associated with embryo development.

To assess attitudes and factors that influence public opinion in the general US population toward insurance coverage and provision of infertility care to lower income patients.

Human endometrium regenerates on a cyclic basis from candidate stem/progenitors whose genetic programs are yet to be determined. A subpopulation of endometrial stromal cells, displaying key properties of mesenchymal stem cells (MSCs), has been characterized. The endometrial MSC (eMSC) is likely the precursor of the endometrial stromal fibroblast. The goal of this study was to determine the transcriptome and signaling pathways in the eMSC to understand its functional phenotype. Endometrial stromal cells from oocyte donors (n = 20) and patients undergoing benign gynecologic surgery (n = 7) were fluorescence-activated cell sorted into MCAM (CD146)+/PDGFRB+(eMSC), MCAM (CD146)−/PDGFRB+(fibroblast), and MCAM (CD146)+/PDGFRB−(endothelial) populations. The eMSC population contained clonogenic cells with a mesenchymal phenotype differentiating into adipocytes when cultured in adipogenic medium. Gene expression profiling using Affymetrix Human Gene 1.0 ST arrays revealed 762 and 1518 significantly differentially expressed genes in eMSCs vs. stromal fibroblasts and eMSCs vs. endothelial cells, respectively. By principal component and hierarchical clustering analyses, eMSCs clustered with fibroblasts and distinctly from endothelial cells. Endometrial MSCs expressed pericyte markers and were localized by immunofluorescence to the perivascular space of endometrial small vessels. Endometrial MSCs also expressed genes involved in angiogenesis/vasculogenesis, steroid hormone/hypoxia responses, inflammation, immunomodulation, cell communication, and proteolysis/inhibition, and exhibited increased Notch, TGFB, IGF, Hedgehog, and G-protein-coupled receptor signaling pathways, characteristic of adult tissue MSC self-renewal and multipotency. Overall, the data support the eMSC as a clonogenic, multipotent pericyte that displays pathways of self-renewal and lineage specification, the potential to respond to conditions during endometrial desquamation and regeneration, and a genetic program predictive of its differentiated lineage, the stromal fibroblast.

Theimplantation process begins with attachment of the trophectoderm (TE) of the blastocyst to the maternal endometrial epithelium. Herein we have investigated the transcriptome of mural TE cells from 13 human blastocysts and compared these with those of human embryonic stem cell (hESC)-derived-TE (hESCtroph). The transcriptomes of hESCtrophat Days 8, 10, and 12 had the greatest consistency with TE. Among genes coding for secreted proteins of the TE of human blastocysts and of hESCtrophare several molecules known to be involved in the implantation process, as well as novel ones, such as CXCL12, HBEGF, inhibin A, DKK3, WNT5A, and follistatin. The similarities between the two lineages underscore some of the known mechanisms and offer discovery of new mechanisms and players in the process of the very early stages of human implantation. We propose that the hESCtrophis a viable functional model of human trophoblasts to study trophoblast-endometrial interactions. Furthermore, the data derived herein offer the promise of novel diagnostics and therapeutics aimed at practical challenges in human infertility and pregnancy disorders associated with abnormal embryonic implantation.

Endometriosis, a benign gynecologic disorder associated with pelvic pain and infertility, is characterized by the presence of endometrial tissue outside the uterus. Disease pathogenesis is poorly understood, although we and others have observed altered gene expression and cellular responses in eutopic endometrial stromal fibroblasts (hESF) and tissue, particularly with respect to secretory endometrium under the influence of progesterone. These findings suggest that women with endometriosis have abnormal eutopic endometrium that could affect embryonic implantation. One cell type of great interest in eutopic endometrium is the CD56-bright uterine natural killer cell (uNK), which normally displays a unique phenotype of low cytotoxic activity and high cytokine/growth factor production. These cells promote angiogenesis in decidualizing endometrium and control of trophoblast invasion. Previous studies characterizing whole transcriptome expression in eutopic endometrium from women with endometriosis highlight reduced expression of uNK-related genes in secretory endometrium, including glycodelin A, granzyme A, and IL-15. Thus, we have hypothesized that uNK cells in endometrium from women with endometriosis differs in abundance, phenotype, and function, compared to uNK from women without disease, and the current study focused on the number of uNK cells in eutopic endometrium from women with vs. without endometriosis. Immunohistochemistry for the uNK marker, CD56, was conducted on endometrial tissues from women with (n=11) and without (n=7) endometriosis in the proliferative and midsecretory phases. Quantification of uNK was achieved by counting immunopositive cells in at least 3 optical fields per sample and normalizing to cellular density using ImageJ analysis software. Across proliferative and midsecretory phases, density of uNK in endometriosis was >50% reduced compared to non-endometriosis (p=0.018), and this difference remained when comparing only midsecretory phase samples (p=0.048). To determine whether the reduced uNK density is due to reduced IL-15 production by hESF, IL-15 (a mitogen for uNK) was measured by ELISA in culture media from hESF from women with (n=6) and without (n=5) disease, cultured for 96h in the presence/absence of 0.5mM cAMP. Endometriotic hESF showed a 70% reduction in IL-15 production in the absence of cAMP and a 60% reduction in the presence of cAMP, although these differences were not statistically significant due to high sample variation. In conclusion, these findings reveal a dramatic reduction in uNK cells in eutopic endometrium from women with endometriosis, which may contribute to infertility and the aberrant endometrial cell behaviors observed with this disorder. Reduction in uNK abundance may not be due solely to differences in IL-15 production by hESF. Therefore, further studies are ongoing to determine what factors from the eutopic endometrium, particularly the decidualized hESF, might contribute to uNK abundance in vivo, and how hESF paracrine signals influence NK cell activation, cytotoxic capacity, and cytokine/growth factor production in vitro.(platform)